Coping and adaptation to dementia family caregiving: A pilot study

Family caregivers of Black older adults with dementia are at risk for cognitive decline and premature death. Reducing this risk and filling the void of culturally responsive interventions for caregivers requires the development of participant informed models of care that promote group strengths such as effective coping. In this pilot study, Black family caregivers (n=30) completed a survey comprised of a demographic questionnaire, various measures of function, self-efficacy, social support, and coping. Study findings point to a well-educated population with underlying health concerns such as obesity, hypertension, and diabetes that may be complicated by caregiving stress. Common coping strategies used by participants included spiritual coping (80%), use of past experiences (80%), and information gathering (75%). Clinicians can support dementia family caregivers by promoting spiritual coping and self-care, as well as providing reference resources about respite and managing challenging behaviors. Power analysis suggests a future sample size of 385.     

2013－2020年江苏省镇江市流感样病例及其病原学监测分析

  目的  了解2013 — 2020年江苏省镇江市流感样病例（ILI）的流行病学特征及流感病毒的病原学变化趋势,为流感的防控提供科学依据。  方法  利用镇江市现有的流感监测哨点医院和流感监测网络实验室进行病例和病原学监测,并对2013 — 2020年的监测数据进行统计分析。  结果  2013 — 2020年镇江市流感监测哨点医院共报告207 252例ILI,年平均ILI百分比（ILI%）为3.50%,总体呈上升趋势（趋势χ2=30 554.00, P<0.001）。 ILI中,0～4、5～14、15～24、25～59、≥60岁年龄组病例分别占39.91%、27.53%、7.40%、17.93%、7.23%。 在同一个流感监测年度内ILI%存在2个高峰（12月至次年2月、6 — 9月）。 2013 — 2020年镇江市共检测ILI标本25 318份,流感阳性标本2 780份,流感病毒检出率为10.98%,甲型流感（检出率为7.08%）的流行强度高于乙型流感（检出率为3.90%）,甲型H1N1流感集中在1 — 3月,甲型H3N2集中在7 — 12月,乙型Victoria系集中在4 — 6月,乙型Yamagata系集中在1 — 3月。 季节性流感病毒的流行存在2个特点:一是以某种型别毒株单独流行为主,二是多种型别毒株混合流行。 2013 — 2019年镇江市共报告39起ILI暴发疫情,其中37起发生在学校和幼托机构,2020年未报告ILI暴发疫情。 2020年新型冠状病毒肺炎防控期间镇江市ILI%（6.82%）较2013 — 2019年均值（3.03%）增加125.08%,并以≥60岁人群增加最多,增幅为176.61%;2020年1月流感病毒检出率为52.21%,2月为11.20%,3月为0.37%,4 — 12月为0,全年检出率（5.37%）比2013 — 2019年均值（11.79%）减少54.41%。  结论  镇江市各级政府及相关部门应根据当地ILI和流感病毒的流行特点,有针对性地加强流感防控工作,2020年新型冠状病毒肺炎防控期间所采取的防控措施值得借鉴。     

β‐Glucan enhances antitumor immune responses by regulating differentiation and function of monocytic myeloid‐derived suppressor cells

Myeloid‐derived suppressor cells (MDSCs) accumulate in tumor‐bearing hosts and play a major role in tumor‐induced immunosuppression, which hampers effective immuno‐therapeutic approaches. β‐Glucans have been reported to function as potent immuno‐modulators to stimulate innate and adaptive immune responses, which contributes to their antitumor property. Here, we investigated the effect of particulate β‐glucans on MDSCs and found that β‐glucan treatment could promote the differentiation of M‐MDSCs (monocytic MDSCs) into a more mature CD11c⁺ F4/80⁺ Ly6C^low population via dectin‐1 pathway in vitro, which is NF‐κB dependent, and the suppressive function of M‐MDSCs was significantly decreased. Treatment of orally administered yeast‐derived particulate β‐glucan drastically downregulated MDSCs but increased the infiltrated DCs and macrophages in tumor‐bearing mice, thus eliciting CTL and Th1 responses, inhibiting the suppressive activity of regulatory T cells, thereby leading to the delayed tumor progression. We show here for the first time that β‐glucans induce the differentiation of MDSCs and inhibit the regulatory function of MDSCs, therefore revealing a novel mechanism for β‐glucans in immunotherapy and suggesting their potential clinical benefit.     

Human papillomavirus was not detected by PCR using multiple consensus primer sets in esophageal adenocarcinomas in Chinese patients

The role of human papillomavirus (HPV) infection in the development of esophageal squamous cell carcinoma is well established; however, there are few reports on the role of HPV in esophageal adenocarcinoma. To evaluate the putative role of HPV infection in esophageal adenocarcinoma, 57 formalin‐fixed, paraffin‐embedded esophageal adenocarcinoma specimens were collected from four hospitals in Shanghai and Anyang, China, between 1999 and 2008. HPV DNA was analyzed using PCR with multiple sets of consensus primers for HPV, GP5+/6+, CPI/CPIIG, SPF₁₀, pU‐1M/pU2R, and pU31B/pU2R. Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), the internal control, was amplified successfully in all 57 specimens. However, HPV amplification was not detected in any specimens with any of the consensus primer sets used. The present study indicates that HPV infection is not likely to be a major factor in the etiology of esophageal adenocarcinoma in the Chinese population. J. Med. Virol. 85: 1053–1057, 2013. © 2013 Wiley Periodicals, Inc.     

Effects of Matrine on JAK-STAT Signaling Transduction Pathways in Bleomycin-Induced Pulmonary Fibrosis

The current study aims to investigate the effects of matrine on the JAK-STAT signaling transduction pathways in bleomycin (BLM)-induced pulmonary fibrosis (PF) and to explore its action mechanism. A total of 72 male C57BL/6 mice were randomized into the control, model, and treatment groups. PF models were established by instilling BLM intratracheally. The treatment group was given daily matrine through gastric lavage. Six mice were sacrificed in each group at 3, 7, 14, and 28 days. The lung tissues were observed using hematoxylin-eosin staining. The expression of JAK, STAT1, and STAT3 was observed using immunohistochemistry and then determined using real-time polymerase chain reaction. Alveolitis and PF significantly improved in the treatment group compared with the model group (P < 0.05). The expression of JAK, STAT1, and STAT3 in the model group increased at day 7, peaked at day 14 and then decreased, but the expression was still higher than that in the control group at day 28 (P < 0.05). The three indices in the treatment group were significantly lower than those in the model group at any detection time point (P < 0.05). PF causes high expression of JAK, STAT1, and STAT3. Matrine exerts an anti-PF effect by inhibiting the JAK-STAT signaling transduction pathways.     

Metabolic profiling in human SH-SY5Y neuronal cells exposed to perfluorooctanoic acid (PFOA)

Perfluorooctanoic acid (PFOA) is an abundant per- and polyfluoroalkyl substance (PFAS) detected in both indoor and outdoor environments. While studies suggest exposure concerns for humans, studies investigating PFOA-induced neurotoxicity are lacking. To address this gap, we exposed differentiated human SH-SY5Y cells to PFOA (0.1 μM up to 500 μM) at different time points (4, 24, 48, and 72 h) and measured cell viability, Casp3/7 activity, ATP levels, ATP synthase enzyme activity, mitochondrial membrane potential, reactive oxygen species (ROS), oxygen consumption rates for mitochondrial stress test (XFe24 Flux analyzer), glucose utilization, and global metabolome profiles to assess the potential for PFOA-induced neurotoxicity. Treatment with 10 or 100 μM PFOA did not compromise cell viability nor induce cytotoxicity to SH-SY5Y cells over a 48-hour exposure period. However, >250 μM PFOA compromised cell viability, induced cytotoxicity, and induced caspase 3/7 activity at 48 h. ATP levels were reduced in cells treated with 400 μM PFOA for 24 and 48 h, and with 100 μM PFOA and higher at 72 h. ATP synthase activity was inhibited by 250 μM PFOA but was unchanged by PFOA treatment at 200 μM or less. Conversely, mitochondrial membrane potential was reduced by >10 μM PFOA after 24 h. Total ROS was increased with 100 μM PFOA and higher after 4 h of exposure. Several mitochondria-related endpoints (basal respiration, ATP production, maximum respiration) were negatively affected at 250 μM PFOA at both 24- and 48-hour exposure, but were unaltered at concentrations of 100 μM PFOA or less. One exception was mitochondrial spare capacity, which was reduced by 100 μM PFOA after 24-hour exposure. Similarly, glycolysis, glycolytic capacity, and glycolytic reserve of SH-SY5Y cells were not altered by 10 nor 100 μM PFOA. Nontargeted metabolomics was conducted in cells treated with either 10 or 100 μM PFOA for 48 h, as these two concentrations were not cytotoxic and 28 metabolites differed among treatments. Notable was that 10 μM PFOA had little effect on the SH-SY5Y metabolome, and the metabolic profile was not statistically different from media nor solvent controls. On the other hand, 100 μM PFOA shifted the metabolic signature of the neuronal cells, leading to reduced abundance of ATP-related metabolites (adenine, nicotinamide), neurotransmitter precursors (DL-tryptophan, l-tyrosine), and metabolites that protect mitochondria during oxidative stress (betaine, orotic acid, and l-acetyl carnitine). We hypothesize that this metabolic signature may be associated with the reduced mitochondrial membrane potential observed at lower PFOA concentrations. Metabolic shifts appear to precede compromised cell viability, cytotoxicity, and apoptosis. This study generates mechanistic knowledge regarding PFOA-induced neurotoxicity, focusing on mitochondrial oxidative respiration and the neuronal metabolome.     

Just an additional hydrogen bond can dramatically reduce the catalytic activity of Bacillus subtilis lipase A I12T mutant: An integration of computational modeling and experimental analysis

Understanding the structural basis and energetic property of hydrogen bonding and its effects on enzymatic activity is fundamentally important for the rational design of specific enzymes with desired biological functions. In the current study, site-directed mutagenesis analysis preliminarily revealed that the amino acid substitution of Ile12 with Thr12 (I12T) dramatically reduced the hydrolytic activity of Bacillus subtilis lipase A. A further computational investigation proposed that the I12T mutation would establish a geometrically perfect hydrogen bond between the mutated Thr12 and catalytic Ser77 of lipase A, which considerably impaired the catalytic capability of lipase A through two distinct but complementary approaches: rigidizing the enzyme active site and lowering the nucleophilic ability of the catalytic residue Ser77. To verify this hypothesis, a homogenous mutation I12S serving as the control to the I12T mutation was created to examine the hydrogen bonding effect on enzymatic activity. It was found that the I12S mutant only suffered from a slight damage in its hydrolytic ability due to absence of the hydrogen bond originally present at the Thr12–Ser77 interface in the I12T mutant, which was further characterized systematically by quantum mechanics/molecular mechanics (QM/MM) modeling, atom-in-molecules (AIM) analysis and molecular dynamics (MD) simulation. It is suggested that the hydrogen bond arising from the I12T mutation in lipase A can considerably reduce the flexibility and mobility of the enzyme active site, thus impairing the catalytic activity of the lipase A I12T mutant remarkably; the activity loss can be, however, largely recovered by replacing Thr residue at the 12th position of I12T mutant with its analog Ser, which is chemically similar to Thr but cannot form effective hydrogen bonding with Ser77.     

Study on stable equilibrium of levitated impeller in rotary pump with passive magnetic bearings

It is widely acknowledged that the permanent maglev cannot achieve stable equilibrium; the authors have developed, however, a stable permanent maglev centrifugal blood pump. Permanent maglev needs no position detection and feedback control of the rotor, nevertheless the eccentric distance (ED) and vibration amplitude (VA) of the levitator have been measured to demonstrate the levitation and to investigate the factors affecting levitation. Permanent maglev centrifugal impeller pump has a rotor and a stator. The rotor is driven by stator coil and levitated by two passive magnetic bearings. The rotor position is measured by four Hall sensors, which are distributed evenly and peripherally on the end of the stator against the magnetic ring of the bearing on the rotor. The voltage differences of the sensors due to different distances between the sensors and the magnetic ring are converted into ED. The results verify that the rotor can be disaffiliated from the stator if the rotating speed and the flow rate of the pump are large enough, that is, the maximal ED will reduce to about half of the gap between the rotor and the stator. In addition, the gap between rotor and stator and the viscosity of the fluid to be pumped also affect levitation. The former has an optimal value of ≈ 2% of the radius of the rotor. For the latter, levitation stability is better with higher viscosity, meaning smaller ED and VA. The pressure to be pumped has no effect on levitation.     

Technical note: A novel impeller TAH using magnetic bearings for load reduction

A novel impeller TAH (total artificial heart), i.e. bi-ventricular assist impeller pumps, has been developed. The device consists of a rotor with motor magnets and two impellers, a stator with motor coil and iron core, and two pump housings. In both sides of the rotor magnets, as well as the stator coil core, a pair of magnetic bearings was devised to partly counteract the attractive forces between the rotor magnets and the stator coil core. This means the magnetic bearings are used for load reduction. On hydrodynamic testing, the two pumps both produced a flow rate as high as 6 l min -1 and the left pump had a pressure head of 150 mm Hg, and that of the right pump was 50 mm Hg. The highest efficiency of the device, including the motor, the two pumps and the controller, reached 14.7%. The device, weighing 250 g, had a length of 80 mm and a diameter of 40 mm at its largest point. Currently in the world, this is a unique TAH, which is electrically powered and driven by a single motor and has only one moving part, can produce either pulsatile or non-pulsatile flow, both pumps eject flow synchronistically by pulsatile mode, and the volume equilibrium of the two pumps can be achieved automatically without the need for control.     

Comparative proteomics reveals essential mechanisms for osmotolerance in Gluconacetobacter diazotrophicus

Plant growth-promoting bacteria are a promising alternative to improve agricultural sustainability. Gluconacetobacter diazotrophicus is an osmotolerant bacterium able to colonize several plant species, including sugarcane, coffee, and rice. Despite its biotechnological potential, the mechanisms controlling such osmotolerance remain unclear. The present study investigated the key mechanisms of resistance to osmotic stress in G. diazotrophicus. The molecular pathways regulated by the stress were investigated by comparative proteomics, and proteins essential for resistance were identified by knock-out mutagenesis. Proteomics analysis led to identify regulatory pathways for osmotic adjustment, de novo saturated fatty acids biosynthesis, and uptake of nutrients. The mutagenesis analysis showed that the lack of AccC protein, an essential component of de novo fatty acid biosynthesis, severely affected G. diazotrophicus resistance to osmotic stress. Additionally, knock-out mutants for nutrients uptake (Δtbdr and ΔoprB) and compatible solutes synthesis (ΔmtlK and ΔotsA) became more sensitive to osmotic stress. Together, our results identified specific genes and mechanisms regulated by osmotic stress in an osmotolerant bacterium, shedding light on the essential role of cell envelope and extracytoplasmic proteins for osmotolerance.